(1) Field of the Invention
The present invention relates to an improved method for diagnosing blood clotting disorders based upon clotting times for a plasma from a patient. In particular, the present invention relates to a method which uses a combination of charts, pooled normal plasma (PNP) as a control and data bases for normal and abnormal clotting in the presence of various clotting or clot inhibiting agents in diagnosing a specific clotting disorder.
(2) Prior Art
In the United States about 1.5 million people per year have a heart attack. About half survive, and most require thrombolytic (clot-dissolving) treatments like tPA and streptokinase. About 500,000 people are hospitalized each year in the U.S. because of pulmonary embolism (clot in blood vessels in the lungs) or deep venous thrombosis (clot in vessels of limbs, often in the legs). About 220,000 people per year have coronary by-pass surgery for treatment of heart disease resulting from clots blocking coronary blood vessels. 50,000 people die each year of pulmonary embolism. 200,000 people die each year of cerebrovascular disease. 50,000 persons in the U.S. population have inherited clotting defects.
Diseases caused by blood clots are among the most common life-threatening medical problems in the United States. Another group of important diseases is caused by failure of blood to clot (e.g. hemophilia); a lot of these are inherited defects, but some are caused by other conditions like cancer, Lupus, or even certain infections that affect the liver and other tissues involved in the production of blood proteins. Clotting diseases are on the increase because they are associated with life style patterns in the western world (obesity, lack of exercise, smoking), and with aging. People are living longer these days and therefore more are entering the high risk age groups. A lot more people are consequently put on oral anticoagulants to counter this trend. New types of treatment are now being developed that make it all the more important to be able to reach decisions quickly on which treatment to use and whether or not it is working properly.
Accurate and rapid diagnosis of diseases caused by clots or clotting defects is therefore a major everyday problem for doctors and medical technologists. Consequently, there is a significant segment of the clinical diagnostic industry dedicated to providing products to meet this demand.
Laboratory diagnosis depends on tests done by technicians to measure how long the patient's blood plasma takes to clot, as compared to normal, and then to find out exactly what is wrong when the plasma does not clot properly. To do this, laboratories buy test kits and diagnostic reagents that are designed to help identify the clotting problem or defect. Some tests are simple; others are complex, need expensive equipment and skilled personnel, and take a lot of technician's time. Other tests are so complicated or so costly in reagents that routine laboratories in hospitals and clinics don't even do them, so they send the blood sample away to a specialty laboratory where the tests are performed by experts for a fee.
Several companies in the medical diagnostic field sell coagulation diagnostic kits. However, these kits are mostly based on technological principles developed in the 1950's and the procedures are frequently seriously flawed. Modernization in technique has come primarily in the form of automation by computer-controlled instruments (coagulometers) that provide increased accuracy and avoid human errors, and reduce technician time, but the test principles are still the same. These new instruments are expensive, particularly in their most automatic form. They handle multiple samples and have built-in micro-processors that perform all the computations of results and comparisons to normal values. For some of the tests needed for monitoring clot dissolving treatments (e.g. urokinase, tPA), additional equipment is needed.
The trend in the industry toward automation has come about due to the high cost of technical time, and the demand for more, faster and better diagnostic testing. As pharmaceutical companies develop totally new drugs the need for more tests, performed more frequently and giving more accurate information to the doctor, will increase substantially. Clot-dissolving products are expected to be among the biggest growth areas in the medical therapy market over the next decade. For example, based on sale after FDA approval, tPA is the most successful new drug ever introduced in the United States. The diagnostic industry is going to have to move in the direction of speedier tests, performed as close as possible to the patient and his or her physician. The needs for certain kinds of tests that monitor, for example, tPA infusion therapy or oral anticoagulant prophylaxis will increase. The same is true for the "replacement" treatments that are now appearing for genetic and acquired clotting defects; these new therapies have only become possible because of genetic engineering technology. There are no satisfactory systematic diagnostic approaches available in the marketplace to meet these needs at the moment. There is a need for such a systematic approach.
The prior art procedures employed in most cases are flawed; they are outdated and have not been optimized to meet the level of critical, quantitative diagnostic need in today's clinical setting. Reagents of uncertain value or giving unreliable results are used on the basis of tradition rather than on the basis of rigorous scientific evaluation. Consequently, it is not possible to reach a correct and accurate diagnosis using many of them, and they do not match up to expectations of the clinician for therapeutic monitoring. The more complex tests available today for monitoring need equipment and skills that are not routinely available, and therefore they are only done in reference lab settings; although the clinician needs these kinds of test results, the procedures are not run often enough to provide the best results. In some cases the current diagnostic reagents are not stable and their shelf lives are not well characterized for today's quantitative tests. The variables that influence the test results, like disease state and therapeutic history, have not been examined sufficiently in most cases to permit these kits and reagents to be used with confidence for quantitative purposes. Quantitative test data is needed when powerful therapies are being applied that can be disastrous in the wrong situation.
The complications faced by the clinician in dealing with these new surgical and medical interventions becoming available for patients, coupled with the complexity of the lab technology, have resulted in a serious communication gap between the two. There is a need for a comprehensive approach to differential diagnostic logic in thrombotic and clotting diseases, in a modern form that makes the system available and understandable to both clinical and laboratory personnel.